Advances in research on rotaviruses have progressed so rapidly that only 25 years separate the discovery of the virus and the development of the first generation of vaccines. Along the way, many studies have demonstrated that rotavirus is the most common cause of severe diarrhea in children. The structure of rotavirus has been dissected to the most detailed resolution of its fine structure. The genetic organization of its 11 segmented genes has been deciphered and the function of each protein defined. Each of the functional steps, from virus replication and cell entry to issues of pathogenesis and mechanisms of immunity, has become a subject of intense investigation. These advances have been furthered by continuing breakthroughs in our ability to understand and work with the virus in the laboratory.